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自分泌成纤维细胞生长因子2增强人脂肪来源间充质干细胞的多能性。

Autocrine fibroblast growth factor 2 increases the multipotentiality of human adipose-derived mesenchymal stem cells.

作者信息

Rider David A, Dombrowski Christian, Sawyer Amber A, Ng Grace H B, Leong David, Hutmacher Dietmar W, Nurcombe Victor, Cool Simon M

机构信息

Laboratory of Stem Cells and Tissue Repair, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore.

出版信息

Stem Cells. 2008 Jun;26(6):1598-608. doi: 10.1634/stemcells.2007-0480. Epub 2008 Mar 20.

DOI:10.1634/stemcells.2007-0480
PMID:18356575
Abstract

Multipotent mesenchymal stem cells (MSCs), first identified in the bone marrow, have subsequently been found in many other tissues, including fat, cartilage, muscle, and bone. Adipose tissue has been identified as an alternative to bone marrow as a source for the isolation of MSCs, as it is neither limited in volume nor as invasive in the harvesting. This study compares the multipotentiality of bone marrow-derived mesenchymal stem cells (BMSCs) with that of adipose-derived mesenchymal stem cells (AMSCs) from 12 age- and sex-matched donors. Phenotypically, the cells are very similar, with only three surface markers, CD106, CD146, and HLA-ABC, differentially expressed in the BMSCs. Although colony-forming units-fibroblastic numbers in BMSCs were higher than in AMSCs, the expression of multiple stem cell-related genes, like that of fibroblast growth factor 2 (FGF2), the Wnt pathway effectors FRAT1 and frizzled 1, and other self-renewal markers, was greater in AMSCs. Furthermore, AMSCs displayed enhanced osteogenic and adipogenic potential, whereas BMSCs formed chondrocytes more readily than AMSCs. However, by removing the effects of proliferation from the experiment, AMSCs no longer out-performed BMSCs in their ability to undergo osteogenic and adipogenic differentiation. Inhibition of the FGF2/fibroblast growth factor receptor 1 signaling pathway demonstrated that FGF2 is required for the proliferation of both AMSCs and BMSCs, yet blocking FGF2 signaling had no direct effect on osteogenic differentiation. Disclosure of potential conflicts of interest is found at the end of this article.

摘要

多能间充质干细胞(MSCs)最初在骨髓中被发现,随后在许多其他组织中也被找到,包括脂肪、软骨、肌肉和骨骼。脂肪组织已被确定为一种可替代骨髓的MSCs分离来源,因为它在体积上不受限制,且采集时侵入性较小。本研究比较了来自12名年龄和性别匹配供体的骨髓间充质干细胞(BMSCs)和脂肪间充质干细胞(AMSCs)的多能性。从表型上看,这些细胞非常相似,只有三种表面标志物,即CD106、CD146和HLA-ABC,在BMSCs中差异表达。虽然BMSCs中的成纤维细胞集落形成单位数量高于AMSCs,但多种干细胞相关基因的表达,如成纤维细胞生长因子2(FGF2)、Wnt信号通路效应分子FRAT1和卷曲蛋白1,以及其他自我更新标志物,在AMSCs中表达更高。此外,AMSCs表现出更强的成骨和成脂潜力,而BMSCs比AMSCs更容易形成软骨细胞。然而,通过在实验中消除增殖的影响,AMSCs在成骨和成脂分化能力方面不再优于BMSCs。对FGF2/成纤维细胞生长因子受体1信号通路的抑制表明,FGF2是AMSCs和BMSCs增殖所必需的,但阻断FGF2信号对成骨分化没有直接影响。潜在利益冲突的披露见本文末尾。

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